Molecular subgrouping of medulloblastoma in pediatric population using the NanoString assay and comparison with immunohistochemistry methods.

PURPOSE: Molecular subgrouping of medulloblastoma has become important due to its impact on risk group stratification. Immunohistochemistry (IHC) has been widely used but it has innate limitations. The NanoString assay has been proposed as an alternative method. This study aims to present the characteristics of medulloblastoma subgrouped by the NanoString assay and to compare the subgrouping results with the IHC method. METHODS: Pediatric patients with histological diagnosis of medulloblastoma who underwent surgery from 2007 to 2021 were included. Clinical characteristics, pathological findings were reviewed. Molecular subgrouping was performed by IHC and by NanoString nCounter Elements TagSets assay. Test for concordance between two methods was made. RESULTS: Among a total of 101 patients analyzed, subgrouping using the NanoString assay resulted in 14 (13.8%) WNT, 20 (19.8%) SHH, 18 (17.8%) Group 3, and 39 (38.6%) Group 4 subgroup cases. Survival analysis revealed the following from best to worse prognosis: WNT, Group 4, SHH, and Group 3. In SHH subgroup the large cell/anaplastic histology was present in 30% of cases. Seventy-one cases were analyzed for concordance between NanoString and IHC. Cohen's kappa value indicated moderate agreement but identification of Groups 3 and 4 with IHC using NPR3 and KCNA1 markers exhibited poor results. CONCLUSIONS: The NanoString assay of Korean medulloblastoma patients revealed a more aggressive clinical course in the SHH subgroup which may be explained by a higher proportion of large cell/anaplastic histology being present in this subgroup. IHC did not distinguish Group 3 or 4 accurately. The NanoString assay may represent a good alternative method for practical use in the clinical field.

Analysis of multi-omics data on the relationship between epigenetic changes and nervous system disorders caused by exposure to environmentally harmful substances.

Environmentally hazardous substances and exposure to these can cause various diseases. Volatile organic compounds can easily evaporate into the atmosphere, thereby exerting toxic effects through either the skin or respiratory tract exposures. Toluene, a neurotoxin, has been widely used in various industries. However, it has a detrimental effect on the nervous system (such as hallucinations or memory impairment), while data on the mechanism underlaying its harmful effects remain limited. Therefore, this study investigates the effect of toluene on the nervous system via epigenetic and genetic changes of toluene-exposed individuals. We identified significant epigenetic changes and confirmed that the affected abnormally expressed genes negatively influenced the nervous system. In particular, we confirmed that the miR-15 family, upregulated by toluene, downregulated ABL2, which could affect the R as signaling pathway resulting in neuronal structural abnormalities. Our study suggests that miR-15a-5p, miR-15b-5p, miR-16-5p, miR-301a-3p, and lncRNA NEAT1 may represent effective epigenomic markers associated with neurodegenerative diseases caused by toluene.

An acquired cerebral arteriovenous malformation after brain abscess treatment: case report and a review of the literature.

A cerebral arteriovenous malformation (AVM) is a congenital and static disease. However, there are increasing reports of acquired AVMs. The pathophysiology of an acquired AVM has not been fully elucidated but the suggested pathophysiology is a combination of genetic abnormalities and inflammatory cytokines caused by previous brain insults. We report a patient who developed an acquired AVM after the treatment for a brain abscess. She underwent Gamma Knife surgery to treat the acquired AVM. It is necessary to understand the characteristics of acquired AVMs and to further research acquired AVMs.

Intracranial juvenile xanthogranuloma in an infant.

Juvenile xanthogranuloma (JXG) is a type of non-Langerhans cell histiocytosis that most commonly manifests as a solitary cutaneous lesion of the head and neck in children. Intracranial JXG is extremely rare. Although it is widely known that JXG skin lesions gradually disappear over time without treatment, treatment guidelines for intracranial JXG have not been established. It is very difficult to predict whether an intracranial lesion is JXG with only a pre-operative imaging work-up without pathologic confirmation. We report a case of the youngest, a 3-month-old male infant with an intracranial extra-axial mass with rapid growth for 2 months. Additionally, we suggest characteristic MRI findings for intracranial extra-axial JXG of a low T2 signal and a kidney bean shape.

Integrated analysis of multi-omics data on epigenetic changes caused by combined exposure to environmental hazards.

Humans are easily exposed to environmentally hazardous factors in industrial sites or daily life. In addition, exposure to various substances and not just one harmful substance is common. However, research on the effects of combined exposure on humans is limited. Therefore, this study examined the effects of combined exposure to volatile organic compounds (VOCs) on the human body. We separated 193 participants into four groups according to their work-related exposure (nonexposure, toluene exposure, toluene and xylene exposure, and toluene, ethylbenzene, and xylene exposure). We then identified the methylation level and long noncoding RNA (lncRNA) levels by omics analyses, and performed an integrated analysis to examine the change of gene expression. Thereafter, the effects of combined exposure to environmental hazards on the human body were investigated and analyzed. Exposure to VOCs was found to negatively affect the development and maintenance of the nervous system. In particular, the MALAT1 lncRNA was found to be significantly reduced in the complex exposure group, and eight genes were significantly downregulated by DNA hypermethylation. The downregulation of these genes could cause a possible decrease in the density of synapses as well as the number and density of dendrites and spines. In summary, we found that increased combined exposure to environmental hazards could lead to additional epigenetic changes, and consequently abnormal dendrites, spines, and synapses, which could damage motor learning or spatial memory. Thus, lncRNA MALAT1 or FMR1 could be novel biomarkers of neurotoxicity to identify the negative health effects of VOC complex exposure.

Extracellular vesicle-associated miR-135b and -135a regulate stemness in Group 4 medulloblastoma cells by targeting angiomotin-like 2.

BACKGROUND: Extracellular vesicles (EVs) secreted by tumours, including exosomes, are important factors that regulate cell-cell interactions in oncogenesis. Although EV studies are ongoing, the biological understanding of EV-miRNAs derived from brain tumour spheroid-forming cells (BTSCs) of medulloblastoma is poor. PURPOSES: We explored the specific cellular miRNAs and EV-miRNAs in medulloblastoma BTSCs to determine their potential biological function. METHODS: Bulk tumor cells (BTCs) and BTSCs were cultured under different conditions from medulloblastoma tissues (N = 10). RESULTS: Twenty-four miRNAs were simultaneously increased in both cells and EVs derived from BTSCs in comparison to BTCs. After inhibition of miR-135b or miR135a which were the most significantly increased in BTSCs, cell viability, self-renewal and stem cell marker expression decreased remarkably. Through integrated analysis of mRNAs and miRNAs data, we found that angiomotin-like 2 (AMOTL2), which was significantly decreased, was targeted by both miR-135b and miR-135a. STAT6 and GPX8 were targeted only by miR-135a. Importantly, low expression of AMOTL2 was significantly associated with overall poor survival in paediatric Group 3 and Group 4 medulloblastoma patients. CONCLUSION: Our results indicated that inhibition of miR-135b or miR-135a leads to suppress stemness of BTSC through modulation of AMOTL2.

Panobinostat, a histone deacetylase inhibitor, rescues the angiogenic potential of endothelial colony-forming cells in moyamoya disease.

PURPOSE: Moyamoya disease (MMD) is one of the most common causes of pediatric stroke. We found defective angiogenic function and downregulation of retinaldehyde dehydrogenase 2 (RALDH2) in MMD endothelial colony-forming cells (ECFCs). Downregulation of RALDH2 mRNA was caused by decreased binding of acetyl-histone H3 (Ac-H3) to the RALDH2 promoter. In this study, we evaluated the feasibility of using a histone deacetylase (HDAC) inhibitor, panobinostat, to upregulate RALDH2 expression and restore the angiogenic potential of MMD ECFCs. METHODS: ECFCs from healthy normal controls and patients with MMD were isolated and characterized. After panobinostat treatment, western blot, tube formation, and chromatin immunoprecipitation (ChIP) assays were conducted in vitro. A matrigel plug assay was performed in vivo. RESULTS: Panobinostat increased the levels of Ac-H3 and Ac-H4 in both normal and MMD ECFCs but was much more effective in MMD ECFCs. Increased expression of RALDH2 by panobinostat was observed only in MMD ECFCs. Panobinostat increased the tube formation of both normal and MMD ECFCs in vitro and in vivo, but the effect was greater with MMD ECFCs. CONCLUSIONS: We demonstrated that panobinostat increases the angiogenic ability of MMD ECFCs by regulating RALDH2 acetylation. Our results suggest that panobinostat might be a potent therapeutic option for MMD patients.

PD-1/PD-L1 and immune-related gene expression pattern in pediatric malignant brain tumors: clinical correlation with survival data in Korean population.

BACKGROUND: PD-L1 expression has been evaluated as a predictive biomarker for immunotherapy in numerous tumor types. However, very limited data are available in pediatric brain tumors. The aim of this study was to characterize PD-1 and PD-L1 expressions of four pediatric malignant brain tumors and gene expression profile. METHODS: This study included 89 pediatric patients receiving standard treatment at Seoul National University Children's Hospital and Seoul National University Bundang Hospital between 1990 and 2014: atypical teratoid/rhabdoid tumor (AT/RT) 20; ependymoma (EPN) 20; high grade glioma (HGG) 21; and medulloblastoma (MBL) 28. We performed immunohistochemistry assays for PD-1 and PD-L1. To characterize the gene expression, a custom immune-response focused gene panel was used. RESULTS: PD-1 expression was positive in 7 (35%) AT/RT, 7 (35%) EPN, 4 (19%) HGG, and 3 (11%) MBL patients. PD-L1 expression was positive in 8 (40%) AT/RT, 4 (20%) EPN, and 4 (19%) HGG; negative in all MBL patients. There was no statistically significant difference in the overall survival of PD-L1 positive patients. The gene expression analysis demonstrated differences in two clustering functional categories: cell-cell signaling and antigen presentation pathway. CONCLUSIONS: AT/RT, EPN, and HGG showed a relatively higher expression rate of PD-L1 (19-40%). This suggests these tumor types might be good candidates for PD-1 checkpoint blockade. We determined that gene expression may potentially serve as a molecular tool in predicting which patients will respond to immunotherapy. Further investigation is required to better understand the predictive and prognostic role of PD-L1 in pediatric brain tumors.

Clinical outcome of pediatric choroid plexus tumors: retrospective analysis from a single institute.

BACKGROUND: Choroid plexus tumor is a rare brain tumor with variable clinical features according to the histological grade. We reviewed the treatment outcome of 23 children, focusing on the biological behavior of the atypical choroid plexus papilloma (ACPP) and the current therapeutic strategy in choroid plexus carcinoma (CPC). METHODS: The demographics, clinical features, surgical treatments, adjuvant therapies, and survival were reviewed. RESULTS: The median age at diagnosis was 18 months--55 months for choroid plexus papilloma (CPP), 8 months for ACPP, and 15 months for CPC. Gross total resections were achieved in seven of eight patients with CPP, seven of seven with ACPP, and three of eight with CPC. Seven patients with CPC received chemotherapy. Four patients received high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (aPBSCT), and three among them have survived. Four patients with CPC received radiotherapy. One CPP patient and one CPC patient underwent radiosurgery. All CPP and ACPP patients have survived. The overall survival rate of the CPC patients was 62.5% in the first year and 42.9% in the second year. The progression-free survival rate of the CPC patients was 50% in the first year and 0% in the second year. Seven patients underwent permanent cerebrospinal fluid diversion surgery because of hydrocephalus or subdural effusion. CONCLUSION: CPP and ACPP were surgically curable. Multi-modal treatments are necessary in the management of CPC with poor prognosis. HDCT and aPBSCT may be important to treat infants for whom radiotherapy is limited. Hydrocephalus and subdural effusion should be resolved with appropriate management.

The Role of Early and Delayed Surgery for Infants with Congenital Brain Tumors.

PURPOSE: The present study aimed to evaluate the role of early and delayed surgery in congenital brain tumors and analyze the clinical outcomes of infantile brain tumors. MATERIALS AND METHODS: We performed a retrospective cohort study on 69 infantile brain tumors at a single institution from January 2008 to June 2023. Outcomes were assessed as early mortality (within 30 days following surgery) to evaluate the risk of early surgery in congenital brain tumors. Outcomes of recurrence and overall survival were analyzed in infantile brain tumors. RESULTS: Surgery-related early mortality appeared to occur in young and low-body-weight patients. Cut-off values of age and body weight were found to be 1.3 months and 5.2 kg to avoid early mortality. Three patients (3/10, 30%) showed early mortality in the early surgery group, and early mortality occurred in one patient (1/14, 7.14%) in the delayed surgery group, whose tumor was excessively enlarged. Younger age at diagnosis (< 3 months of age; hazard ratios [HR], 7.1; 95% confidence intervals [CI], 1.4 to 35.6; p=0.018) and leptomeningeal seeding (LMS; HR, 30.6; 95% CI, 3.7 to 253.1; p=0.002) were significant independent risk factors for high mortality in infantile brain tumors. CONCLUSION: We suggest delaying surgery until the patient reaches 1.3 months of age and weighs over 5.2 kg with short-term imaging follow-up unless tumors grow rapidly in congenital brain tumors. Younger ages and the presence of LMS are independent risk factors for high mortality in infantile brain tumors.

Neurocognitive outcomes and associated clinical factors 5 years after surgery in children with craniosynostosis.

OBJECTIVE: Craniosynostosis involves early closure of one or more sutures, which is known to limit normal cranium growth and interfere with normal brain development. Various surgical methods are used, ranging from minimally invasive strip craniectomy to more extensive whole-vault cranioplasty. This study aimed to evaluate neurocognitive outcomes 5 years after surgical treatment in children with craniosynostosis and to evaluate relevant clinical factors. METHODS: After exclusion of genetically confirmed syndromic craniosynostosis patients, a retrospective review was conducted on 112 nonsyndromic craniosynostosis patients who underwent surgical treatment and follow-up neurocognitive assessment. Ninety-seven patients underwent strip craniectomy with postoperative orthotic helmet therapy, and 15 received other surgical treatment: 4 with distraction osteotomy and 11 with craniofacial reconstruction. Neurocognitive assessment using the Korean Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (K-WPPSI-IV), was performed 5 years postoperatively. Clinical factors were assessed regarding neurocognitive outcomes. RESULTS: The mean age at surgery was significantly younger in the strip craniectomy group (strip craniectomy 4.6 months vs other surgical treatment 18.6 months, p < 0.01). Patients with 2 or more sutures involved were more likely to receive more extensive surgical treatment (16.5% in the strip craniectomy group vs 53.8% in the other group, p < 0.01). Four (3.5%) patients who showed evidence of increased intracranial pressure (ICP) also underwent more extensive surgical treatment. Multivariable linear regression revealed a significant correlation of age at neurocognitive testing (-3.18, 95% CI -5.95 to -0.40, p = 0.02), increased ICP (-34.73, 95% CI -51.04 to -18.41, p < 0.01), and the level of maternal education (6.11, 95% CI 1.01-11.20, p = 0.02) with the Full-Scale Intelligence Quotient (FSIQ). Age at surgery, involvement of 2 or more sutures, and type of operation demonstrated no correlation with FSIQ. Among the 97 patients who underwent strip craniectomy, the FSIQ ranged from mean ± SD 100.2 ± 10.2 (bicoronal) to 110.1 ± 12.7 (lambdoid), and there was no significant difference between the suture groups (p = 0.41). The 5 index scores were all within average ranges based on their age norms. CONCLUSIONS: Age at neurocognitive assessment, increased ICP, and maternal education level showed significant correlations with the neurocognitive function of craniosynostosis patients. Although children with craniosynostosis exhibited favorable 5-year postoperative neurocognitive outcomes across various synostosis sutures, longer follow-up is needed to reveal the incidence of neurocognitive dysfunction in these patients.

Comprehensive multiomics analysis reveals distinct differences between pediatric choroid plexus papilloma and carcinoma.

Choroid plexus tumors (CPTs) are intraventricular tumors derived from the choroid plexus epithelium and occur frequently in children. The aim of this study was to investigate the genomic and epigenomic characteristics of CPT and identify the differences between choroid plexus papilloma (CPP) and choroid plexus carcinoma (CPC). We conducted multiomics analyses of 20 CPT patients including CPP and CPC. Multiomics analysis included whole-genome sequencing, whole-transcriptome sequencing, and methylation sequencing. Mutually exclusive TP53 and EPHA7 point mutations, coupled with the amplification of chromosome 1, were exclusively identified in CPC. In contrast, amplification of chromosome 9 was specific to CPP. Differential gene expression analysis uncovered a significant overexpression of genes related to cell cycle regulation and epithelial-mesenchymal transition pathways in CPC compared to CPP. Overexpression of genes associated with tumor metastasis and progression was observed in the CPC subgroup with leptomeningeal dissemination. Furthermore, methylation profiling unveiled hypomethylation in major repeat regions, including long interspersed nuclear elements, short interspersed nuclear elements, long terminal repeats, and retrotransposons in CPC compared to CPP, implying that the loss of epigenetic silencing of transposable elements may play a role in tumorigenesis of CPC. Finally, the differential expression of AK1, regulated by both genomic and epigenomic factors, emerged as a potential contributing factor to the histological difference of CPP against CPC. Our results suggest pronounced genomic and epigenomic disparities between CPP and CPC, providing insights into the pathogenesis of CPT at the molecular level.

Clinical Outcome of Endoscopic Procedure in Patients with Shunt Malfunction.

OBJECTIVE: The goal of this study was to analyze the clinical outcomes of endoscopic third ventriculostomy (ETV) and endoscopic septostomy when shunt malfunction occurs in a patient who has previously undergone placement of a ventriculoperitoneal shunt. METHODS: From 2001 to 2020 at Seoul National University Children's Hospital, patients who underwent ETV or endoscopic septostomy for shunt malfunction were retrospectively analyzed. Initial diagnosis (etiology of hydrocephalus), age at first shunt insertion, age at endoscopic procedure, magnetic resonance or computed tomography image, subsequent shunting data, and follow-up period were included. RESULTS: Thirty-six patients were included in this retrospective study. Twenty-nine patients, 18 males and 11 females, with shunt malfunction underwent ETV. At the time of shunting, the age ranged from 1 day to 15.4 years (mean, 2.4 years). The mean age at the time of ETV was 13.1 years (range, 0.7 to 29.6 years). Nineteen patients remained shunt revision free. The 5-year shunt revisionfree survival rate was 69% (95% confidence interval [CI], 0.54-0.88). Seven patients, three males and four females, with shunt malfunction underwent endoscopic septostomy. At the time of shunting, the age ranged from 0.2 to 12 years (mean, 3.9 years). The mean age at the time of endoscopic septostomy was 11.9 years (range, 0.5 to 29.5 years). Four patients remained free of shunt revision or addition. The 5-year shunt revision-free survival rate was 57% (95% CI, 0.3-1.0). There were no complications associated with the endoscopic procedures. CONCLUSION: The results of our study demonstrate that ETV or endoscopic septostomy can be effective and safe in patients with shunt malfunction.

Long-Term Surgical Outcome of Indirect Bypass Surgery in Young Children With Moyamoya Disease.

BACKGROUND: The prognosis of moyamoya disease (MMD) in young children (younger than 4 years) is worse than that of older adults. The effectiveness of surgery is still inconclusive. OBJECTIVE: To evaluate long-term outcomes after indirect bypass in young children with MMD. METHODS: A total of 1417 MMD children underwent indirect bypass from August 1988 to October 2020. This study included 135 patients who were younger than 4 years at the time of surgery. The clinical features and surgical outcomes of these patients were assessed. We analyzed the long-term outcome of 102 children who were followed up for more than 5 years (mean: 18.8 years, range: 5-27.3 years). Cross-sectional analysis was performed to evaluate overall outcomes based on the Lansky Play Performance Scale (LPS). The annual risk of symptomatic stroke after surgery was calculated with a person-year method, and the event-free survival rate was evaluated using the Kaplan-Meier method. RESULTS: The overall clinical outcome was favorable (LPS ≥ 80) in 88% of the patients. The overall postoperative adverse event rate was 15%, including 1 death. At the last follow-up, 86% of patients who had seizures at diagnosis were seizure-free. During the follow-up, there were 3 symptomatic infarctions on the operated hemisphere (postoperative 3, 3, and 10 months each). There was no hemorrhagic event. The annual infarction rate was 0.16% per person-year. The 20-year event-free survival rates for symptomatic infarction were 97%. CONCLUSION: Indirect bypass could provide a satisfactory long-term outcome and prevent recurrent stroke in young children with MMD.

Comparison of Bifrontal Craniotomy and Multiple Burr Hole Encephalogaleoperiosteal-Synangiosis for Pediatric Moyamoya Disease: An Experience of 346 Patients.

BACKGROUND AND OBJECTIVES: Moyamoya disease (MMD) is a steno-occlusive disease treated with revascularization surgery. Craniotomy and multiple burr hole encephalogaleoperiosteal-synangiosis (EGPS) are used for revascularization of the anterior cerebral artery territory. The aim of this study was to compare the clinical outcome between the 2 surgical methods in pediatric patients with MMD. METHODS: A retrospective review of patients with MMD who underwent bifrontal indirect bypass surgery was performed. Clinical features, perioperative data, and angiographic, perfusion, and functional outcomes were compared between the 2 groups. Propensity score matching was performed to compare the perioperative characteristics and clinical outcomes. RESULTS: A total of 346 patients were included in this study, 111 patients underwent bifrontal craniotomy EGPS, and 235 patients had bifrontal multiple burr hole EGPS. An insignificant higher rate of postoperative infarction (11.7% vs 5.5%, P = .072) and more postoperative hemorrhage occurred in the craniotomy EGPS group (3.6% vs 0%, P = .004). Of the 83 patients selected with propensity score matching for each group, the duration of operation was shorter ( P < .001) and the amount of intraoperative bleeding was significantly less in the multiple burr hole EGPS group ( P = .008). There was no difference in clinical outcomes between the 2 groups. CONCLUSION: Bifrontal multiple burr hole EGPS has benefits over craniotomy with shorter surgical time, less intraoperative bleeding, fewer postoperative complications, and comparable perfusion and functional outcomes. Multiple burr hole EGPS is a safe and effective method that might be considered for revascularization of the anterior cerebral artery territory in pediatric patients with MMD.

Cyclin-Dependent Kinase Inhibitor 2A is a Key Regulator of Cell Cycle Arrest and Senescence in Endothelial Colony-Forming Cells in Moyamoya Disease.

OBJECTIVE: Endothelial colony-forming cells (ECFCs) have been reported to play an important role in the pathogenesis of moyamoya disease (MMD). We have previously observed stagnant growth in MMD ECFCs with functional impairment of tubule formation. We aimed to verify the key regulators and related signaling pathways involved in the functional defects of MMD ECFCs. METHODS: ECFCs were cultured from peripheral blood mononuclear cells of healthy volunteers (normal) and MMD patients. Low-density lipoproteins uptake, flow cytometry, high content screening, senescence-associated ß-galactosidase, immunofluorescence, cell cycle, tubule formation, microarray, real-time quantitative polymerase chain reaction, small interfering RNA transfection, and western blot analyses were performed. RESULTS: The acquisition of cells that can be cultured for a long time with the characteristics of late ECFCs was significantly lower in the MMD patients than the normal. Importantly, the MMD ECFCs showed decreased cellular proliferation with G1 cell cycle arrest and cellular senescence compared to the normal ECFCs. A pathway enrichment analysis demonstrated that the cell cycle pathway was the major enriched pathway, which is consistent with the results of the functional analysis of ECFCs. Among the genes associated with the cell cycle, cyclin-dependent kinase inhibitor 2A (CDKN2A) showed the highest expression in MMD ECFCs. Knockdown of CDKN2A in MMD ECFCs enhanced proliferation by reducing G1 cell cycle arrest and inhibiting senescence through the regulation of CDK4 and phospho retinoblastoma protein. CONCLUSION: Our study suggests that CDKN2A plays an important role in the growth retardation of MMD ECFCs by inducing cell cycle arrest and senescence.

Surgical indication of pediatric Rathke's cleft cyst based on a 20-year retrospective cohort.

OBJECTIVE: Rathke's cleft cyst (RCC) is the most commonly encountered pituitary incidentaloma in children. Because RCC is not frequently diagnosed in children, there are few reports on pediatric RCCs. The natural course of the disease and appropriate treatments are still obscure. The present study aimed to elucidate the natural history and surgical indications of RCCs in children. METHODS: The authors retrospectively reviewed the clinical presentations, imaging features, ophthalmological evaluations, endocrine evaluations, and surgical outcomes of pediatric RCCs at a single institution from January 2000 to October 2022. Clinical outcomes between the surgery and observation groups were compared. RESULTS: Among 93 patients, there were 41 patients in the surgery group and 52 patients in the observation group. The mean age at diagnosis was 10.9 years, and the mean follow-up period was 5.6 years. Headache fully or partially improved after surgery (86.2%), but the rate of improvement was not different from that of the observation group (70.0%). Ophthalmological abnormalities were effectively improved by surgical treatment (93.3%). Both the improvement and deterioration rates of endocrine abnormalities were significantly higher in the surgery group (p = 0.026 and p < 0.001, respectively), but the deterioration rate (43.9%) was higher than the improvement rate (14.6%). In the surgery group, the recurrence rate was 17.1% and the reoperation rate was 4.9%. Compared with total cyst wall resection, cyst fenestration with partial wall resection was associated with a higher recurrence rate (26.9%, p = 0.035) but a lower rate of endocrine abnormalities (30.8%, p = 0.049). CONCLUSIONS: Pediatric RCCs of ≥ 10 mm in size were analyzed. Ophthalmological abnormalities are the major surgical indications for pediatric RCCs. Headache and partial endocrine abnormalities may be improved with surgery, but they are not absolute indications for surgery. Cyst fenestration with partial wall resection via an endoscopic endonasal approach is the most recommended surgical method. Follow-up is essential to monitor for the occurrence of visual field defects and the recurrence of cysts.

Survival and Malignant Transformation of Pineal Parenchymal Tumors: A 30-Year Retrospective Analysis in a Single-Institution.

BACKGROUND: This study aims to elucidate clinical features, therapeutic strategies, and prognosis of pineal parenchymal tumors (PPT) by analyzing a 30-year dataset of a single institution. METHODS: We reviewed data from 43 patients diagnosed with PPT at Seoul National University Hospital between 1990 and 2020. We performed survival analyses and assessed prognostic factors. RESULTS: The cohort included 10 patients with pineocytoma (PC), 13 with pineal parenchymal tumor of intermediate differentiation (PPTID), and 20 with pineoblastoma (PB). Most patients presented with hydrocephalus at diagnosis. Most patients underwent an endoscopic third ventriculostomy and biopsy, with some undergoing additional resection after diagnosis confirmation. Radiotherapy was administered with a high prevalence of gamma knife radiosurgery for PC and PPTID, and craniospinal irradiation for PB. Chemotherapy was essential in the treatment of grade 3 PPTID and PB. The 5-year progression-free survival rates for PC, grade 2 PPTID, grade 3 PPTID, and PB were 100%, 83.3%, 0%, and 40%, respectively, and the 5-year overall survival rates were 100%, 100%, 40%, and 55%, respectively. High-grade tumor histology was associated with lower survival rates. Significant prognostic factors varied among tumor types, with World Health Organization (WHO) grade and leptomeningeal seeding (LMS) for PPTID, and the extent of resection and LMS for PB. Three patients experienced malignant transformations. CONCLUSION: This study underscores the prognostic significance of WHO grades in PPT. It is necessary to provide specific treatment according to tumor grade. Grade 3 PPTID showed a poor prognosis. Potential LMS and malignant transformations necessitate aggressive multimodal treatment and close-interval screening.

Identification of bacterial pathogens in brain abscesses by metagenomic approach using nanopore 16S amplicon sequencing.

Brain abscess is medically challenging. In this study, we applied nanopore sequencing for 16S rRNA analysis and investigated its efficacy and diagnostic value for patients with brain abscesses. Genomic DNA was extracted from the pus samples (n = 27) of brain abscess, and 16S rRNA genes were amplified by PCR. Sequencing libraries were generated using a rapid barcoding kit, and the generated reads were analyzed using the EPI2ME16S workflow. A conventional culture study was performed. More sensitive identification of pathogens was made by 16S sequencing, faster than the culture study. The proportion of anaerobic bacteria identified by 16S sequencing was higher (75%) than that obtained by culturing (32%). Polymicrobial infections were identified in 10 cases (40%) by 16S sequencing, while the culture study identified multiple bacteria in only 2 cases (8%). 16S sequencing was useful for identifying the composition of polymicrobial infections, including rare pathogens, and for the initial diagnosis of space-occupying lesions.

The return of an old worm: cerebral paragonimiasis presenting with intracerebral hemorrhage.

Paragonimiasis is caused by ingesting crustaceans, which are the intermediate hosts of Paragonimus. The involvement of the brain was a common presentation in Korea decades ago, but it becomes much less frequent in domestic medical practices. We observed a rare case of cerebral paragonimiasis manifesting with intracerebral hemorrhage. A 10-yr-old girl presented with sudden-onset dysarthria, right facial palsy and clumsiness of the right hand. Brain imaging showed acute intracerebral hemorrhage in the left frontal area. An occult vascular malformation or small arteriovenous malformation compressed by the hematoma was initially suspected. The lesion progressed for over 2 months until a delayed surgery was undertaken. Pathologic examination was consistent with cerebral paragonimiasis. After chemotherapy with praziquantel, the patient was monitored without neurological deficits or seizure attacks for 6 months. This case alerts practicing clinicians to the domestic transmission of a forgotten parasitic disease due to environmental changes.